Interactions between cyclosporine and newer antidepressant medications.
The favorable safety profile of the newer antidepressant drugs recently introduced has lead to their increased use in transplant recipients. These new agents are a chemically diverse group of compounds that have selective serotonin reuptake inhibitory properties. Most of these medications inhibit one or more hepatic microsomal cytochrome p450 isoenzymes. Because cyclosporine is metabolized predominantly by CYP3A3/4 isoenzymes, inhibition of this system can lead to the buildup of toxic levels. Two case reports of cyclosporine toxicity attributable to interactions with the novel antidepressants nefazodone and fluvoxamine are presented. The serum creatinine and whole blood cyclosporine levels were found to be elevated at a routine clinic visit. Although it was subsequently possible to reduce the dose of cyclosporine by between 33% and 50%, the frequency of blood draws and consultations was greatly increased in both patients over several weeks, resulting in considerable patient anxiety. Interestingly, both nefazodone and fluvoxamine are known to potently inhibit the CYP3A3/4 isoenzymes. It is concluded that the introduction of a novel antidepressant to a cyclosporine-treated allograft recipient may be complicated by cyclosporine toxicity. Intensive monitoring of the serum creatinine and cyclosporine level is indicated under such circumstances, with dose reductions performed as indicated.
Vella
J P
JP
Laboratory of Immunogenetics and Transplantation, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. jpvella@bics.bwh.harvard.edu
Sayegh
M H
MH
D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects*; D016572:Cyclosporine / Q000009:adverse effects*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D014230:Triazoles / Q000009:adverse effects*
D018687:Antidepressive Agents, Second-Generation; D016572:Cyclosporine; D065607:Cytochrome P-450 Enzyme Inhibitors; D016666:Fluvoxamine; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; C051752:nefazodone